Bronchiolitis obliterans with organizing pneumonia (BOOP) describes a long observed, but unclassific pattern of acute lung injury. In humans, BOOP is characterized by fibrosis of small airways with fibroi extension into the alveolar spaces with preservation of alveolar ducts and walls. It is frequently associated with peribronchiolar organizing pneumonia. The lesions may also be accompanied by lipid-laden foamy alveol macrophages trapped in the air spaces by the fibrosis and by a T cell rich lymphocytic interstitial infiltrate in the regions of the lung directly affected by the lesion. Damage to the alveolar epithelium directly affected by tl BOOP lesion is evident. In addition to hyperplasia of the type H epithelial cells, necrosis and sloughing epithelial cells has been observed and is thought to result in the partial alveolar collapse seen in human BOOK Since the classification of BOOP as a distinct clinical syndrome, increasing numbers of reports of BOOP ha' appeared in the clinical literature and it is now accepted that BOOP is a clinically significant pulmona syndrome. While BOOP can be associated with documented viral and bacterial infections, many cases are n associated with know causes and are thus classified as idiopathic. An experimental small animal model of BOC has not been described in the literature. Thus, little is know concerning the pathogenesis and treatment of this disorder. While a number of small animal models are available for other fibrotic lung diseases, the pattern fibrosis elicited in these diseases does not resemble that observed in BOOP. Therefore, while these models a of interest for the study of interstitial lung fibrosis they are not directly relevant for the study of BOOP. We have described the first small animal model of BOOP in which CBA/J mice infected with reovirus serotyj I/strain Lang develop BOOP lesions which closely resemble the histopathological picture of human BOC described above. In addition, the development of BOOP lesiens in CBA/J mice is virus strain specifi Thus, this model offers the further advantage of allowing a genetic analysis of the viral gene(s) responsible for the induction of BOOP lesions. We propose to utilize the reovirus model to systematically address the hypothesis that (i) the degree of severity of the initial lung injury is a critical determinant in the progression towards BOOP; and (ii) that damage and/or infection of resident pulmonary cellular populations (type 1 and/ type 2 alveolar cells and/or the basement membrane) by reovirus causes the production of a unique pattern pro- inflammatory cytokines which contribute to the characteristic fibrotic lesions associated with BOOP.